What is Gluten Cross-Reactivity?

Since many people with celiac disease continue to feel sick, even when they eliminate gluten from their diet, scientists have been looking for the reason why. One theory is cross-reactivity. What does that mean? When your body develops an allergy to gluten, it creates antibodies that remember gluten’s protein structure. If you eat gluten, those antibodies set off an inflammatory response. Some other foods have similar protein structures to gluten, and you may react to those as if they were gluten. It’s basically a case of mistaken identify. It’s important to note, however, that cross-reactivity isn’t something that happens to everyone. And very few people cross-react to all of the potential foods. It’s simply something to explore when giving up gluten isn’t enough.

Confusion About Which Foods Might Cross-React

There are many lists floating around the internet, and some have probably made their way into your news feed. They aren’t all accurate. In fact, I would say that most aren’t accurate. Why is that so?

Cyrex Labs has a blood test called Array 4, which is highly respected in the alternative health and paleo communities. It tests your blood against 24 foods for potential cross-reaction. Many people have typed up the Cyrex list into a graphic and circulated it around the internet (or reproduced it in articles on various websites). However, they usually simplify the list for easy viewing, and they drop some important details. For example, most lists say that chocolate is a cross-reactor, but if you look at Cyrex’s list, you’ll see they test milk chocolate, not dairy-free chocolate. This is because cocoa doesn’t cross-react; it’s the dairy that has the potential to cross-react. Here’s the Cyrex list: Gluten Grains (as a controlled comparison: rye, barley, spelt and polish wheat); Dairy (both whole milk and 4 isolated proteins); Milk Chocolate, Oats, Yeast, Coffee, Sesame, Buckwheat, Sorghum, Millet, Hemp, Amaranth, Quinoa; Tapioca (also called yucca and cassava); Teff, Soy, Egg, Corn, Rice, Potato.

However, Cyrex’s list isn’t necessarily accurate. When it comes to science, studies published in peer reviewed journals (not private labs) are the benchmark. In fact, Sarah Ballantyne, author of The Paleo Approach, didn’t include any recommendations in her book that weren’t validated in the scientific literature. In 2013, the journal Food and Nutrition Sciences published a study which tested the Cyrex theory, to see if their list of foods really were potential cross-reactors. They even expanded their tests slightly. They went ahead and tested both cocoa and milk chocolate. They also tested regular coffee and instant coffee. Results? They found that only a small portion of the Cyrex list had cross-reactive potential:

Gluten cross-reactivity could only apply to people with celiac disease, not people who are simply sensitive to gluten, because only celiacs have circulating anti-gluten antibodies.

The scientific study didn’t use rigorous testing or reporting standards, which weakens the validity of its findings.

She doesn’t believe gluten cross-reactivity exists. However, she agreed that people with celiac disease might want to avoid the final list from the study for different reasons: (1) Lactose and casein (components of dairy) are common food allergens themselves. (2) Instant coffee, oats and millet are often contaminated with actual gluten. (3) Corn and rice can elicit other inflammatory reactions. (4) When it came to yeast, the authors of the study apparently said they didn’t know if they saw a true cross-reaction, or if their sample was contaminated with gluten. They used brewer’s yeast in the sample, which is often a byproduct of beer.

How it Affects the AIP

The Paleo Approach. Sarah Ballantyne includes information about gluten cross-reactivity in her book, The Paleo Approach. She follows the shorter list above, excerpted from the study published in Food and Nutrition Sciences. You’ll note that all of the foods in that list, with the exception of yeast, are excluded on the AIP already, for other reasons: The AIP is dairy-free, grain-free and seed-free.

What about Yeast? The authors of the study actually said they weren’t sure yeast was a cross-reactor; that their sample might have been contaminated with gluten. I also asked Sarah about this. She said that yeast cross-reaction is rare, and she feels that the benefits of fermented foods (which contain yeast) are more important to autoimmune healing than the minimal risk of consuming yeast. Therefore, yeast is allowed on the AIP, but if you don’t see positive results, you can eliminate that later as a potential troubleshooting step.

What about Tapioca? This is the most common question we are asked as AIP bloggers, when it comes to potential gluten cross-reactive foods. Although tapioca is listed on the Cyrex Array lab test, it wasn’t shown to be cross-reactive in the peer-reviewed study. For that reason, Sarah Ballantyne allows it on the AIP and you will see it in AIP recipes, such as the delicious Crispy Dill Fried Fish on this website.

Should We Ever Reintroduce These Foods? At the start of this article, I mentioned that these foods are potential cross-reactors. That means it depends on the person. None of the foods on this list are eaten on a strict paleo diet anyway. However, if you have celiac disease and would like to expand your diet beyond strict paleo, just be mindful that your body might respond to them more strongly than others. For that reason, it would be best to reintroduce other foods first, and postpone these until later in your reintroduction process. Both Mickey and Angie have celiac disease, and they have both reintroduced white rice successfully. Mickey cannot tolerate dairy in any form, but Angie can tolerate some. In your own reintroduction process, you’ll find which foods do and don’t work for you.

Eileen Laird of Phoenix Helix has been living the paleo lifestyle since June 2012, reducing her rheumatoid arthritis symptoms by 95% without any steroid or immunosuppressant medication. Merging straight talk with inspiration and information, Eileen strives to help us all live the autoimmune life well! She believes in the power of symbolism: the phoenix represents our ability to transform; the helix represents the power we have over the expression of our genes. In addition to her blog, she hosts the only paleo podcast dedicated to autoimmune healing. She also hosts a weekly AIP Recipe Roundtable, is the author of the e-book Reintroducing Foods on the AIP, and you can find her on Facebook and Pinterest.

31 comments

Great post! I have looked into this too and have called and discussed with Doctors who consult for Cyrex. After asking the question about whether or not Array 4 should be extrapolated to anyone with Celiac or Gluten sensitivity I received this answer:

“The gluten associated cross reactive foods were only tested against alpha-gliadin-33, so in that regard we do not know if these foods cross react with any other gluten peptides (like gamma-gliadin). So the cross-reactive potential of Array 4 would currently only apply to an individual who has positive alpha-gliadin-33 antibodies. Although the article mainly addresses CD we would extrapolate the information to a person with NCGS with positive alpha-gliadin-33 antibodies who is refractory to a gluten-free diet.”

Please note that they studied “cross reactive potential” specifically for a subgroup of CELIAC patients who tested positive for alpha-gliadin-33 antibodies ONLY. Whether or not those of us who may be gluten sensitive have any cross reactive potential with any of these foods is, at this time, purely extrapolation.

Anne, can you share the identity or credentials of the individuals who provided the information that gluten associated cross reactive foods were only tested against alpha gliadin 33? Thank you Eileen for this detailed important discussion and also to Anne for commenting. This information is helpful as I learn about cross reactivity. I am amazed. I am so glad Anne thought to ask this insightful question about Array 4 being extrapolated to anyone with Celiac or Gluten sensitivity. I never tested but gained enormous health benefits by eliminating gluten, then dairy, then corn, then soy, then eggs. Without verifiable information to tell me if I am sensitive to alpha gliandin 33, the expense of cyrex testing might be a complete waste. Does it make sense to eat gluten in order test for alpha gliadin 33? After reading your comment, it seems it may be better test for cross reactivity or sensitivity to listed offending foods (many of which I have been consuming) by another elimination diet. Save money on labs and spend it on organic autoimmune paleo food.

Hi Meryl, While I don’t have an answer to your specific question (maybe Anne can chime in here) I agree with your perspective to spend money on food vs. lab testing. Often, one of these tests cost what it would take to feed ourselves this way for a month or two, and often giving us more accurate information about how our bodies are interacting with certain foods!

I want to clear up a major misunderstanding about Cyrex Array 4. I’ve personally had this done and I’ve seen the clinical guide that Cyrex gives to practitioners. The name of the array is “Gluten-Associated Cross-Reactive Foods and Foods Sensitivity” and the confusion comes in when assuming that all 24 foods are classified as potential cross-reactors.

The fact is that Cyrex only lists those same foods that the Food and Nutrition Sciences study found to be cross-reactors as being cross-reactors (so, the study confirmed, rather than debunked Cyrex). The rest of the foods on the panel are simply foods commonly found on a gluten-free diet. The purpose of the panel is to kill two birds with one stone: find cross-reactive foods and regular sensitivities to foods that people on GF diets have probably replaced gluten with. So, eggs, potato, tapioca, teff, etc. are not considered cross-reactive by Cyrex (they really ought to change the name!).

Thanks for sharing that, Erin! You are right that they should change the title. Even Dr. Amy Myers and Dr. David Perlmutter have listed all the foods on the Array 4 as cross-reactive. So much unnecessary confusion!

Thankfully, the list is pretty short! It’s such a helpful test to do right before embarking on AIP because if certain foods do test cross-reactive, you know not to even go there with trying to reintroduce those! For me, casein and whey were positive, but not milk butyrophyllin, so I knew that certified brands of casein-free ghee were still safe 🙂

I’m excited for you that you do well with ghee. Many people do (but some don’t) and it often has nothing to do with cross-reactivity. I wrote an article about food sensitivity testing and how it often has both false positives and negatives, so it’s best to confirm those results with elimination/provocation. I don’t recommend people eat or avoid foods based on tests alone.

Hi Jillian, Not sure the point you are trying to make here–it is true I did not react well to ghee, but not true I have not tried other dairy products. Dairy and I have a long history, with a misdiagnosis of severe asthma as a child that turned out to be an anaphylactic reaction to the small amounts of dairy in my diet (I never ate milk, cheese, yogurt, etc. as a child because it “grossed me out”, but I think deep down my body knew).

Considering this history, I was not surprised that ghee didn’t work for me, even the cultured kind, which can work for a lot of people with dairy protein allergies. Since anaphylaxis is not fun, I now choose not to eat it even though I *might* tolerate it in certain forms. Since going AIP I suspect I have been exposed to cross-contamination without a bad reaction, but I don’t want to push it.

Thanks for writing this fantastic article! I love cassava and am excited to know it is allowed on AIP as I am a chef and cook for others also on AIP. One thing I wanted to mention though is that you got yucca mixed up with yuca. This happens often and I am very aware of it now since I used to be confused myself and I wanted to make sure I knew the difference. Yuca is cassava/manioc/tapioca, while yucca is a different plant and they are botanically unrelated. Yucca looks similar to the agave plant (as they are in the same family), grows in arid environments, and has spiky sword-shaped leaves. Yuca grows in tropical climates. I’ve never tried them but the leaves of cassava are edible and apparently high in lysine.

[…] “Since many people with celiac disease continue to feel sick, even when they eliminate gluten from their diet, scientists have been looking for the reason why. One theory is cross-reactivity. What does that mean? When your body develops an allergy to gluten, it creates antibodies that remember gluten’s protein structure. If you eat gluten, those antibodies set off an inflammatory response. Some other foods have similar protein structures to gluten, and you may react to those as if they were gluten. It’s basically a case of mistaken identify. It’s important to note, however, that cross-reactivity isn’t something that happens to everyone. And very few people cross-react to all of the potential foods. It’s simply something to explore when giving up gluten isn’t enough.” What Is Gluten Cross-Reactivity? – Autoimmune Paleo […]

[…] Trace Allergens – High quality ghee companies like Tin Star Foods and Pure Indian Foods have their ghee tested to be certified casein-free and lactose-free. The problem is that the lab equipment isn’t sensitive enough to pick up all the tiny particles that may remain. Here’s a quote from Pure Indian Foods: “Our ghee is batch tested to be no more than 0.25% lactose and 2.5 ppm casein/whey.” That’s as precise as lab equipment can get, and at this level, they’re allowed to call it 100% casein and lactose free. To give you a comparison, the standard for gluten-free labeling is less than 20ppm, so this is a very small amount milk solids remaining. However, just as there are “sensitive celiacs” who react to trace amounts of gluten, there are people sensitive enough to dairy to react to these trace amounts as well. In addition, the protein structure of gluten and dairy are close enough that the body can sometimes mistake one for the other (gluten cross-reactivity). […]

[…] Gluten Cross-Reaction – The theory that some other proteins have a similar structure that the body can mis-identify as gluten. Dr. Fasano doesn’t believe this exists. Instead, he thinks the other food reactions are caused by leaky gut. […]

I do NOT have celiac but battle Hashimotos and my functional doctor who trained under Dr. K had me do the Cyrex Array 4 test and now there is a more extensive Cyrex Array test that she has recommended. But after reading this post, I am not sure if I should pay the $600+ if in reality the tests isn’t completely accurate for someone like me where it seems cross-re activity doesn’t really exist. My original question before reading the post was, does the Cyrex Array tests line up with with what people find when they do the AIP diet and elimination and reintroduction of foods? I didn’t want to waste trying to reintroduce a food I haven’t been eating because of my results from this test showing I had a reaction to it anyway. But now is that even accurate? Obviously I will talk with my doctor about this but curious if anyone else, not Celiac that also had the array 4 test found any validity to it with the AIP foods?

Hi Robyn, I can’t really say since I haven’t done the test. Elimination and reintroduction is still the gold standard, and many people miss things with these tests (and get anxious about other things that don’t turn up to be problems). Personally, I am very happy with my choice not to test and instead spend that money on real food!

My daughter and I also both react to canola oil, quinoa, and arrow root. In an effort to recover from During’s disease, I haven’t eaten any grains whatsoever for the past year and a half, also no sugar, iodized salt, or potatoes. I miss food.

After being on AIP for 3 months I and really doing well without issues. I had dandelion greens mixed in with other mixed greens from my local organic market. I had a reaction to the dandelion greens, and wondering if others have experienced the same issue? I have heard that others with gluten issues have also had issues with this green. What is your take and why does this happen?

Can anyone answer whether camels milk has the same genetic make up / situation as other dairy? My daughter and I are stuck. We both love coconut / rice milk due to the sweetness and thickness. However I think I have a problem with the arsenic in the rice possibly and or cross reaction. I’m / we might both be nut allergic and soy milk tastes horrible to us. Has anyone checked the situation with camels milk? Now available in uk. Bit worried about trying if I’m going to cross react. They say it has less lactose. Thanks

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